Endoscopy in the Age of GLP-1 RAs: 2024 Sees New Risk-Based Perioperative Guidance

The recent rise of GLP-1 receptor agonists (GLP-1 RAs) has been nothing short of revolutionary for the field of medicine, with no other class of medications matching their profound impact across multiple disciplines.

Since they were first introduced in 2005 with the US Food and Drug Administration (FDA) approval of exenatide (Byetta) for type 2 diabetes, GLP-1 RAs have exploded in popularity, now boasting additional indications for cardiovascular risk reduction and weight management. Nearly 2 decades after their debut, the excitement around GLP-1 RAs shows no signs of stopping as the class continues to be studied for use in heart failure, kidney disease, and more.¹

Despite their solidified position at the forefront of therapeutic innovation and subsequent rapid growth in popularity, significant gastrointestinal concerns have arisen, particularly regarding their effects on gastric motility and the potential complications they pose for endoscopic procedures.

“Though GLP-1 RAs are commonly used for diabetes and obesity management, the indications are rapidly increasing… there is no question that the use of these drugs will increase rapidly in the near future,” Girish Joshi, MD, a professor of anesthesiology and pain management at the University of Texas Southwestern Medical School, explained to HCPLive, describing the delayed gastric emptying associated with this class of drugs and the potential for aspiration as the biggest concerns facing anesthesiologists. “Although the incidence [of aspiration] may be relatively low, the consequences are significant, and that is something that needs to be emphasized.”

How Did We Get Here? A Look at the Rise of GLP-1 RAs

GLP-1 RAs’ rise to fame dates back to 2005 with the FDA approval of exenatide (Byetta) as adjunctive therapy to improve blood sugar control in patients with type 2 diabetes who have not achieved adequate control on metformin and/or a sulfonylurea. Since then, 6 other GLP-1 RAs have received approval and come to market, the most recent being Novo Nordisk’s semaglutide (Ozempic; Wegovy).¹

Semaglutide received FDA approval in 2017 as an adjunct to diet and exercise for improving glycemic control in adults with type 2 diabetes.2 It would later go on to earn additional approvals for cardiovascular risk reduction in adults with type 2 diabetes and known cardiovascular disease in 2020; chronic weight management in adults with obesity or overweight with ≥1 weight-related condition in 2021; and most recently, cardiovascular risk reduction in adults with obesity or overweight and established cardiovascular disease in 2024.^3,4,5

A recent analysis of NHANES data found more than half of US adults—approximately 137 million—are candidates for semaglutide based on its current indications. Beyond the approvals semaglutide already boasts, recent studies have suggested it can also provide benefits for patients with obesity-related heart failure with preserved ejection fraction, osteoarthritis, and kidney disease in people without diabetes.⁶

“Most people who take care of patients will have some knowledge of GLP-1s,” Andrew Wang, MD, chief of the section of interventional endoscopy in the division of gastroenterology and hepatology and director of interventional endoscopy at the University of Virginia, told HCPLive. “They are incredibly popular in the lay media, as well as in medical circles.”

Growing Perioperative Concerns

While GLP-1 RAs, particularly semaglutide, appear to offer transformative benefits across an increasing number of disease spaces, their ascent in clinical use has been accompanied by growing concerns about their potential to induce delayed gastric emptying, nausea, and other GI complications, raising critical questions among gastroenterologists and endoscopists navigating this evolving landscape.

In 2023, the American Society of Anesthesiologists (ASA) Task Force on Preoperative Fasting released guidance based on a review of available literature on GLP-1 RAs and associated gastrointestinal adverse effects, acknowledging limited evidence on the preoperative management of these drugs to prevent regurgitation and pulmonary aspiration of gastric contents at the time of publication.⁷

Citing concerns about GLP-1 RA-induced delayed gastric emptying and associated high risk of regurgitation and aspiration of gastric contents, the guidance suggested holding GLP-1 RAs prior to the procedure/surgery, irrespective of the indication, dose, or the type of procedure/surgery.⁷

“Keep in mind this could mean different things for different medications. Liraglutide is taken every day, so you hold the medication the day before. That's easy to remember, but semaglutide and tirzepatide are weekly injections, so patients had to remember to hold it the week before their endoscopy,” Violeta Popov, MD, PhD, director of bariatric endoscopy at the VA NY Harbor Healthcare System, explained to HCPLive in an interview at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting, citing the potential impact on the treatment of patients’ diabetes, their glucose levels, and the subsequent safety of these procedures.⁸ “This guidance changed practices all over the country. Patients were canceled for procedures if they didn't hold the GLP-1 RA, depending on the institution.”

Joshi, an author of the 2023 ASA guidance, told HCPLive the primary aim at that time was to notify anesthesiologists and the public that there was concern about the use of GLP-1 RAs in the context of procedures/surgeries.

“We gave some guidance for holding the drug, but now we have more data to help us identify the specific patient populations that are at risk, and that allows us to approach this at-risk population more specifically,” Joshi explained.

Out With the Old, In With the New: 2024 Sees Revised Guidance

In October of 2024, the ASA released updated clinical guidance on the use of GLP-1 RAs prior to elective surgery and gastrointestinal endoscopies, this time in collaboration with the American Society for Metabolic and Bariatric Surgery, American Gastroenterological Association, International Society of Perioperative Care of Patients with Obesity, and Society of American Gastrointestinal and Endoscopic Surgeons.^9,10

Citing inconsistencies in prior clinical care documents and subsequent uncertainty about how to provide safe, effective, and disease-equitable surgical and procedural care to patients taking GLP-1RAs, the authors recognized the need for guidance regarding the use of these drugs in the perioperative period, even with limited data available to construct evidence-based guidelines.^9,10

Contrary to the previous 2023 guidance from ASA, the new multisociety guidance published in 2024 suggests most patients can continue to safely take GLP-1 RA therapy prior to their procedure/surgery and therefore do not need to hold the medication. Specifically, the updated guidance recommends basing the use of GLP-1 RAs in the perioperative period on shared decision-making between the patient and procedural, anesthesia, and prescribing care teams while balancing the metabolic need for the GLP-1RA with individual patient risk.^9,10

“Most of my patients are unaware of the potential risks posed by GLP-1 RAs, as this is such a new and emerging area of study. Personally, I inform my patients about the potential concerns as well as the inconclusive/lack of data that is currently available so that we can come to a joint decision based on their individual risk factors and preferences,” Adelina Hung, MD, a clinical assistant professor at Rosalind Franklin University Chicago Medical School and director of the IBD program at Sinai Health System Chicago, told HCPLive, noting her standard of care is most aligned with the newest multisociety guidance and that different choices may be made for different patients.

“I think this multi-society guidance document is very timely because it's coming in an era where we're learning more, but there's a lot of confusion based on different societal documents,” Wang explained. “We tried to seek a middle ground where one of the focuses is on a multidisciplinary approach that includes shared decision-making with the patient and keeping the patient the center focus.”

Joshi was careful to note that the evidence supporting the guidance was low, saying “I'm glad that several of the societies came together and so that way now we are on the same page, but this is more for consensus because we are still working with low-quality evidence and a small number of studies.”

Despite the limited evidence available for this iteration of the guidance, Wang pointed to new research that is already coming out about this topic to eventually support evidence-based guidelines. However, he noted even more research will be necessary in the future as other agents with different potencies and side effects become available.

“The more we learn about this, the better,” Joshi said. “It's important to find the right balance in terms of caring for the patient long-term and managing his or her diabetes or cardiovascular risk, but also trying to get them safely through their endoscopic procedures.”

References

1. Biopharma PEG. Evolution of GLP‐1 receptor agonists for diabetes treatment. Biopharma PEG. September 22, 2022. Accessed December 3, 2024. https://www.biochempeg.com/article/299.html.
2. Kunzmann K. FDA Approves Semaglutide (OZEMPIC) for T2D Glycemic Control. HCPLive. December 5, 2017. Accessed December 3, 2024. https://www.hcplive.com/view/fda-approves-ozempic-for-type-2-diabetes-glycemic-control
3. Kunzmann K. FDA Approves Semaglutide Injection for Cardiovascular Risk Reduction. HCPLive. January 16, 2020. Accessed December 3, 2024. https://www.hcplive.com/view/fda-approves-ozempic-for-type-2-diabetes-glycemic-control
4. Kunzmann K. FDA Approves Semaglutide Injection for Cardiovascular Risk Reduction. HCPLive. June 4, 2021. Accessed December 3, 2024. https://www.hcplive.com/view/fda-approves-semaglutide-obesity-weight-management
5. Campbell P. Semaglutide (Wegovy) Receives FDA Label Expansion to Include Cardiovascular Risk Reduction. HCPLive. March 8, 2024. Accessed December 3, 2024. https://www.hcplive.com/view/semaglutide-wegovy-receives-fda-label-expansion-to-include-cardiovascular-risk-reduction
6. Campbell P. More than 50% of US Adults Considered Eligible for Semaglutide with Current Labeling. HCPLive. November 18, 2024. Accessed December 3, 2024. https://www.hcplive.com/view/more-than-50-of-us-adults-considered-eligible-for-semaglutide-with-current-labeling
7. American Society of Anesthesiologists. American Society of Anesthesiologists Consensus-Based Guidance on Preoperative Management of Patients (Adults and Children) on Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists. June 29, 2023. Accessed December 3, 2024. https://www.asahq.org/about-asa/newsroom/news-releases/2023/06/american-society-of-anesthesiologists-consensus-based-guidance-on-preoperative
8. Brooks A. Violeta Popov, MD, PhD: Do GLP-1 RAs Need to Be Held Before Endoscopy? HCPLive. October 30, 2024. Accessed December 3, 2024. https://www.hcplive.com/view/violeta-popov-md-phd-do-glp-1-ras-need-to-be-held-before-endoscopy
9. American Gastroenterological Association. Most patients can continue GLP-1 anti-obesity drugs before surgery. October 29, 2024. Accessed December 3, 2024. https://gastro.org/press-releases/most-patients-can-continue-glp-1-anti-obesity-drugs-before-surgery-2/
10. Kindel TL, Wang AY, Wadwah A, et al. Multisociety Clinical Practice Guidance for the Safe Use of Glucagon-like Peptide-1 Receptor Agonists in the Perioperative Period. Clinical Gastroenterology and Hepatology. doi:10.1016/j.cgh.2024.10.003